Under this application for continued support several studies now in progress will be continued in the Hematology Research Laboratories of Cleveland Metropolitan General Hospital -- all studies are related to erythrocyte production and destruction. Vitamin B12 deficiency has been induced in Rhesus monkeys by dietary manipulation under controlled circumstances. Although no hematologic changes have yet occurred, amblyopia, optic atrophy, papillo-macula bundle degeneration, and hind limb spasticity have occurred -- only in deficient animals and those supplemented with folic acid. Biochemical studies will be carried out concerning lipid analysis of nerve tissue and various Vitamin B12- dependent enzymes. Beginning, intermediate, and final stages of the sol- gel transformation of deoxygenated S hemoglobin have been delineated by continuous monitoring of viscosity. Laser light scattering studies and electron microscopy will now be combined with viscosity to characterize the aggregates present at the various stages. In B6-responsive sideroblastic anemias, the interrelationships of tryptophan with pyridoxal phosphate (and pyridoxal phosphokinase) will be examined with respect to hematopoieses.